Targeted drugs work by ‘targeting’ differences that a cancer cell has that make them different from normal cells. Pembrolizumab is a type of cancer drug called a monoclonal antibody. It helps the immune system attack the cancer and stop it from growing.

Lenvatinib (Lenvima) is also a targeted drug. It works by blocking certain proteins that help cells to grow new blood vessels. All cancer cells need blood vessels to survive and grow.

Everyone taking part in this trial has 1 of the following:

pembrolizumab, lenvatinib and chemotherapy (arm 1)

pembrolizumab, dummy drug and chemotherapy (arm 2)

The chemotherapy treatment includes pemetrexed and either cisplatin or carboplatin. Your doctor can tell you which treatment is best for you.

The main aims of this trial are to:

find out how well pembrolizumab, lenvatinib and chemotherapy work as a treatment for advanced NSCLC

learn more about the side effects

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

you are willing to use reliable contraception during treatment and for up to 6 months afterwards

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

your cancer has receptors for a protein called epidermal growth factor (EGFR positive). Your doctor can tell you more about this

you have cancer spread in your brain, spinal cord or the membranes surrounding the brain (carcinomatous meningitis) unless you have had treatment, it has been stable for the past month and you have stopped taking steroids more than 2 weeks ago

your cancer has spread to a major blood vessel and your doctor thinks that you have a high risk of bleeding

you have had chemotherapy, targeted drugs or any other treatment for advanced NSCLC

you have had pembrolizumab, lenvatinib or any other similar drug

you have had radiotherapy in the past 2 weeks and still have moderate or severe side effects from it, or you have had radiotherapy in the past week if it was radiotherapy to help with symptoms (palliative)

are taking part in another clinical trial or have taken part in a trial looking at a new drug or device in the last month

have or have had lung problems such as pneumonitis

have an autoimmune disease that needed treatment that reached your whole body (systemic) in the past 2 years unless it was treatment to replace something that the body makes such as thyroxine or insulin

take or have taken drugs that damp down your immune system such as steroids in the past week unless it was a very small dose

have problems with your gut and can’t absorb capsules

have heart problems such as an abnormal heart rhythm, congestive heart failure, angina that isn’t stable or you have had a heart attack in the past year

have had an organ transplant from a donor

have protein in your urine

have HIV

have hepatitis B or hepatitis C

have active tuberculosis

have coughed up a large amount of blood in the past 2 weeks

have an active infection that needs antibiotics that reach your whole body (systemic)

have side effects from previous medical treatments

have any other serious medical condition or mental health problem that the trial team think could affect you taking part

Other

You cannot join this trial if any of these apply. You:

are pregnant or breastfeeding

are sensitive to any of the drugs used in this trial or anything they contain

have had a live vaccine in the last month

Trial design

This is an international phase 3 trial. Researchers hope that around 714 people worldwide and 45 people from the UK will agree to take part.

It is a randomised trial. The people taking part are put into 1 of the following groups at random:

pembrolizumab, lenvatinib and chemotherapy

pembrolizumab, dummy drug (placebo) and chemotherapy

Neither you nor your doctor are able to decide which group you are in. And neither you nor your doctor will know which group you are in. This is a double blind trial.

have cisplatin or carboplatin as a drip into your bloodstream on day 1

have pemetrexed as a drip into your bloodstream on day 1

take lenvatinib as capsules that you swallow whole every day

After 4 cycles of treatment, you stop having cisplatin or carboplatin. You continue to have pembrolizumab, pemetrexed and lenvatinib. This is called maintenance treatment. You have this every 3 weeks.

You have maintenance treatment for as long as it is working, and the side effects aren’t too bad. You can have up to 35 pembrolizumab treatments.

You have regular tests to check how well the treatment is working. You might stop treatment if tests show that your cancer has disappeared. You may start a second course of pembrolizumab and lenvatinib if your cancer comes back after this. Your doctor can tell you more about this.

Pembrolizumab, dummy drug and chemotherapy (arm 2)

You have 4 cycles of treatment, taking about 3 months in total. You have each cycle in the following way. You:

have pembrolizumab as a drip into your bloodstream on day 1

have cisplatin or carboplatin as a drip into your bloodstream on day 1

have pemetrexed as a drip into your bloodstream on day 1

take a dummy drug as capsules that you swallow whole every day

After 4 cycles of treatment, you stop having cisplatin or carboplatin. And continue to have pembrolizumab, pemetrexed and dummy drug every 3 weeks (maintenance treatment).

You continue to have maintenance treatment for as long as it is working, and the side effects aren’t too bad. You can have up to 35 pembrolizumab treatments.

You may also be able to have a second course of treatment with pembrolizumab and dummy drug if your cancer comes back after you stop treatment. Your doctor can tell you more about this.

Hospital visits

During treatment, you see the trial team on day 1 and day 15 of your treatment cycle. This continues for 2 months. You then see the trial team every 3 weeks. You have blood tests and a physical examination every time you see them.

You have a CT scan every 6 weeks for 4 months. You then have a CT scan:

every 9 weeks for a year

then every 12 weeks for a year

This continues for as long as the treatment is helping you and the side effects aren’t too bad.

When you finish treatment, you see the trial team after a month. You then see or speak with the trial team every 3 months.

Side effects

The trial team monitor you during treatment and afterwards. You have a phone number to call them if you are worried about anything. The team will tell you about all the possible side effects before you start the treatment.

Pembrolizumab and lenvatinib affect the immune system. This may cause inflammation in different parts of the body which can cause serious side effects. Side effects can happen during treatment or some months after treatment has finished.

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